1. Field of the Invention
The present invention relates to biodegradable aliphatic polyesters. In some embodiments, the biodegradable aliphatic polyester is grafted with poly(ethylene glycol) having reactive groups. In some embodiments, the biodegradable aliphatic polyester is applied to matrices for drug delivery systems and biochips.
2. Background Art
Aliphatic polyesters generally exhibit excellent biodegradability. For this reason, research on applications of aliphatic polyesters as medical polymers, such as matrices for drug delivery systems, scaffolds for tissue engineering, medical sutures and water-absorbing materials have been actively studied. Representative aliphatic polyesters used in various medical fields include polycaprolactone, polylactide and copolymers thereof. However, several disadvantages of aliphatic polyesters exist due to their high hydrophobicity and crystallinity. These disadvantages include adsorption of proteins to the polymer matrix, denaturation of proteins contained in the polymers, and local accumulation of acidic hydrolysates. Due to these disadvantages, extensive research has been undertaken to impart hydrophilicity to the aliphatic polyesters.
Aliphatic polyesters combined and copolymerized with hydrophilic materials such as poly(ethylene glycol), poly(vinyl alcohol) or heparin have been suggested. Among them, a copolymer with poly(ethylene glycol) has been widely studied. Block, star and graft copolymers in which hydrophobic chains are covalently bound with hydrophilic chains have been reported to exhibit peculiar dispersion characteristics in aqueous solutions. Additionally, these copolymers have shown improved protein stability and blood compatibility.
Various processes for synthesizing block copolymers have been proposed. For example, synthesis of a block copolymer can be carried out by ring-opening polymerization of a cyclic compound of an aliphatic ester (hereinafter, referred to as an “alicyclic ester compound”) with a mono-alkoxy poly(ethylene glycol) in the presence of a ring-opening catalyst. Star-shaped copolymers can be prepared in a similar manner. Graft copolymers can typically be prepared by reacting mono-alkoxy poly(ethylene glycol) with epichlorohydrin (Williamson reaction) to synthesize epoxy poly(ethylene glycol) macromers. Copolymerization of epoxy poly(ethylene glycol) and alicyclic ester compounds occurs by a ring opening reaction.
Although modified aliphatic polyesters produced by the above methods exhibit improved hydrophilicity and reduced crystallinity, further modification is limited. The limitation is due to the difficulty to reacting the alkoxy groups at the end of the poly(ethylene glycol) chains with another functional group.
Most research on aliphatic polyesters grafted with hydroxyl group-terminated poly(ethylene glycol) has followed two approaches. In one approach, poly(ethylene glycol) methacrylate is added to a linear aliphatic polyester. The mixture is then subjected to reactive extrusion to produce a polymer having hydroxyl group-terminated grafted chains. Another approach is based on the modification of an alicyclic ester compound. A monomeric alicyclic ester compound, in which the hydroxyl group is blocked by a protecting group, is ring-opened in the presence of a catalyst. After the polymerization, the protecting group is removed and the hydroxyl group is reacted with a poly(ethylene glycol) derivative to produce an aliphatic polyester containing poly(ethylene glycol) having a hydroxyl group at the end of the chain.
Thus, the aliphatic polyesters have an advantage in terms of the functionality in hydroxyl groups at the terminals of the grafted poly(ethylene glycol) chains. However, the process has several drawbacks. For example, the backbone of the aliphatic polyester can be degraded during the reactive extrusion. As a result, the molecular weight of the polyester is reduced. Additionally, in the case of using modified monomer, it is difficult to increase the content of the poly(ethylene glycol) in the aliphatic polyester, since the graft ratio of poly(ethylene glycol) is dependent on the ratio of the modified monomer to the main chain.